Testing the Addition of Total Ablative Therapy to Usual Systemic Therapy Treatment for Limited Metastatic Colorectal Cancer, ERASur Trial

Inclusion Criteria:

* Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom)
* PRE-REGISTRATION (STEP 0): Pathologically proven diagnosis of metastatic colorectal adenocarcinoma with metastases (biopsy from primary tumor or metastatic site is acceptable)
* PRE-REGISTRATION (STEP 0): No known microsatellite instable (MSI) tumor
* PRE-REGISTRATION (STEP 0): No known BRAF V600E mutation
* PRE-REGISTRATION (STEP 0): Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. No known peritoneal and/or omental metastases. If radiologic studies suggest the presence of peritoneal disease, a diagnostic laparoscopy is recommended to verify the absence of peritoneal implants
* PRE-REGISTRATION (STEP 0): Liver-only metastatic disease on baseline imaging prior to starting chemotherapy is NOT permitted. For patients with liver metastases, there must be at least one other site of metastasis in addition to the liver on initial imaging to be eligible for this study. Of note, patients who have metastatic disease to the liver and at least one other site on initial imaging who have liver-only metastatic disease on subsequent imaging after completing initial systemic therapy are eligible
* PRE-REGISTRATION (STEP 0): Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
* REGISTRATION (STEP 1): Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* REGISTRATION (STEP 1): Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* REGISTRATION (STEP 1): A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
* REGISTRATION (STEP 1): Patients must have no overt evidence of disease progression during systemic therapy prior to registration
* REGISTRATION (STEP 1): Not eligible for hepatic artery infusion pump (HAIP) therapy or benefit of HAIP therapy is undefined
* REGISTRATION (STEP 1): Primary tumor is already resected OR patient has had a clinical complete response without surgical resection and no local regrowth (primary rectal tumors only) OR primary tumor is amenable to surgical resection, as determined by consultation and documentation with surgeon or documentation of discussion in the institutional multi-disciplinary tumor board where a surgeon confirms resectability. Patients with unresectable primary tumors are not eligible
* REGISTRATION (STEP 1): Four (4) or fewer apparent sites of metastatic disease based on review by local medical team of radiographic imaging obtained following at least 12 weeks of systemic therapy. Of note, the primary tumor and associated regional lymph nodes do not count as one of the sites of disease.

  * Sites of metastatic disease must be radiographically evident, but pathologic confirmation is not required.
  * Metastatic lesions must be amenable to surgical resection, microwave ablation, radiationSABR or any combination of these modalities.
  * Subcentimeter indeterminate lesions such as lung nodules \< 5 mm in size may be considered metastases unless there are \> 2 months of documented stability prior to the initiation of systemic
  * Single sites include:

    * Each hemiliver (right and left), each lobe of the lungs, each adrenal gland, lymph nodes amenable to a single resection or treatment in a single SABR field, bone metastases amenable to treatment in a single SABR field.
* REGISTRATION (STEP 1): Patients must have measurable disease per RECIST v1.1
* REGISTRATION (STEP 1): Patients must be receiving (or have received) first-line systemic therapy for metastatic disease for a minimum of 12 weeks and a maximum of 52 weeks
* REGISTRATION (STEP 1): Prior definitive therapy, including adjuvant chemotherapy, must have been completed at least 6 months prior to diagnosis of metastatic disease
* REGISTRATION (STEP 1): Not pregnant and not nursing, because this study involves an agent or treatment that has known genotoxic, mutagenic, and teratogenic effects.

  \* Therefore, for women of childbearing potential only, a negative pregnancy test done =\< 14 days prior to registration is required
* REGISTRATION (STEP 1): Age \>= 18 years
* REGISTRATION (STEP 1): Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
* REGISTRATION (STEP 1): Absolute neutrophil count (ANC) \>= 1,000/mm\^3
* REGISTRATION (STEP 1): Platelet count \>= 50,000/mm\^3
* REGISTRATION (STEP 1): Creatinine =\< 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance \>= 30 mL/min

  \* Calculated using the Cockcroft-Gault equation
* REGISTRATION (STEP 1): Total bilirubin =\< 1.5 x ULN

  \* If Gilbert's disease, use direct bilirubin instead of total bilirubin; direct bilirubin =\< 1.5 ULN if patient to receive FOLFIRI (leucovorin calcium, 5-fluorouracil, and irinotecan); direct bilirubin ≤ 3.0 x ULN if patient to receive mFOLFOX6 (leucovorin calcium, 5-fluorouracil, and oxaliplatin)
* REGISTRATION (STEP 1): Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase \[SGOT\]) / alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x ULN

  \* In the event of metastatic liver disease, =\< 5 x ULN
* REGISTRATION (STEP 1): Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Note: HIV testing is not required for eligibility
* REGISTRATION (STEP 1): No other planned concurrent investigational agents while on study

Exclusion Criteria:

* N/A