TAS-102 and Oxaliplatin for the Treatment of Refractory Stage IV Colon Cancer

Inclusion Criteria:

* Histologically confirmed stage IV colon cancer (American Joint Committee on Cancer \[AJCC\] 7th edition) that has progressed after standard therapy that included fluorouracil (5-FU), irinotecan, oxaliplatin, bevacizumab (unless contraindicated) and an anti-EGFR antibody, if RAS wild type. Patients who could not tolerate standard agents because of unacceptable, but reversible toxicity necessitating their discontinuation will be allowed to participate
* Patients who had received adjuvant chemotherapy and had recurrence during or within 6 months of completion of the adjuvant chemotherapy will be allowed to count the adjuvant therapy as one chemotherapy regimen
* Progression of disease must be documented on the most recent scan
* Presence of measurable disease
* RAS mutation and mismatch repair deficiency (MMR) status must be determined (or tissue availability for testing if not already determined)
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Life expectancy of at least 3 months
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
* Hemoglobin \>= 9 g/dL
* Platelets (PLT) \>= 75 x 10\^9/L
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 5 x upper limit of normal (ULN)
* Adequate contraception if applicable
* Women who are nursing and discontinue nursing prior to enrollment in the program
* Ability to take oral medication (i.e., no feeding tube)
* Patient able and willing to comply with study procedures as per protocol
* Patient able to understand and willing to sign and date the written voluntary informed consent form (ICF) at screening visit prior to any protocol-specific procedures

Exclusion Criteria:

* Patients who have previously received TAS-102
* Grade 2 or higher peripheral neuropathy (functional impairment)
* Symptomatic central nervous system (CNS) metastases requiring treatment
* Other active malignancy within the last 3 years (except for non-melanoma skin cancer or a non-invasive/in situ cancer)
* Pregnancy or breast feeding
* Current therapy with other investigational agents
* Active infection with body temperature \>= 38 degree Celsius (C) due to infection
* Major surgery within prior 4 weeks (the surgical incision should be fully healed prior to drug administration)
* Any anticancer therapy within prior 3 weeks of first dose of study drug
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to TAS-102
* Current therapy with other investigational agents or participation in another clinical study or any investigational agent received within prior 4 weeks
* Grade 3 or higher hypersensitivity reaction to oxaliplatin, or grade 1-2 hypersensitivity reaction to oxaliplatin not controlled with pre-medication
* Has unresolved toxicity of greater than or equal to Common Terminology Criteria for Adverse (CTCAE) grade 2 attributed to any prior therapies (excluding anemia, alopecia, skin pigmentation, and platinum-induced neurotoxicity)