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There is no further treatment option for metastatic colon patients who are refractory to standard chemotherapy and to whom novel biological agents are not available. We evaluated the outcomes of mitomycin-C, 5-fluorouracil (5-FU) and leucovorin in patients with metastatic colon cancer previously treated with oxaliplatin/5-FU/leucovorin and irinotecan/5-FU/leucovorin.We retrospectively analyzed 46 patients who had received mitomycin-C/5FU/leucovorin between March 2008 and December 2009. All patients had failed prior first-line and second-line therapy containing oxaliplatin, irinotecan, and 5-FU.The median age of the patients was 57.0 years (range, 34.0–76.0) and their median Eastern Cooperative Oncology Group performance status was 1 (0–2). A complete or partial response was not observed in any patient and stable disease was observed in 19 patients (41.3%). The median duration of follow up was 29 weeks (range 8–87 weeks). Median progression-free survival was 10 weeks (95% CI 8–12) and median overall survival was 38 weeks (95% CI 32–44). Grade 3 and 4 hematological toxicities included neutropenia in five patients (10.8%) and thrombocytopenia in four patients (8.8%). Grade 3 or 4 non-hematologic toxicities included nausea and vomiting in two patients. There were no treatment-related deaths.The combination regimen of mitomycin-C/5-FU/leucovorin showed marginal activity and tolerable toxicity profiles in heavily pretreated metastatic colorectal cancer patients.