CPI-613 and Fluorouracil in Treating Patients With Metastatic Colorectal Cancer That Cannot Be Removed by Surgery

Inclusion Criteria: * Histologically and cytologically confirmed metastatic colorectal adenocarcinoma (colon, rectal or colorectal cancer) that is not resectable * Have failed or have not tolerated FOLFOX, FOLFIRI and, if KRAS wild type, then a EGFR inhibitor-based regimen * Eastern Cooperative Oncology Group (ECOG) performance status being 0-2 * Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted contraceptive methods (abstinence, intrauterine device \[IUD\], oral contraceptive or double barrier device) during the study, and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation * Fertile men must practice effective contraceptive methods during the study, unless documentation of infertility exists * At least 2 weeks must have elapsed from any prior surgery * Granulocyte count \>= 1500/mm\^3 * White blood cell (WBC) \>= 3500 cells/mm\^3 or \>= 3.5 bil/L * Platelet count \>= 100,000 cells/mm\^3 or \>= 100 bil/L * Absolute neutrophil count (ANC) \>= 1500 cells/mm\^3 or \>= 1.5 bil/L * Hemoglobin \>= 9 g/dL or \>= 90 g/L * Aspartate aminotransferase (AST/serum glutamic oxaloacetic transaminase \[SGOT\]) =\< 3 x upper normal limit (UNL), alanine aminotransferase (ALT/serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x UNL (=\< 5 x UNL if liver metastases present) * Bilirubin =\< 1.5 x UNL * Serum creatinine =\< 1.5 mg/dL or 13 umol/L * International normalized ratio or INR m…