The aim of this study was to evaluate the efficacy and tolerance of second-line continuous 5-fluorouracil (5FU) chemotherapy combined with folinic acid and mitomycin C in patients with advanced colorectal cancer who progressed on first-line chemotherapy. From June 1992 to April 1994, 24 consecutive patients, median age 59.7 years (range 41-73), performance status (PS) 0 to 2, were treated as second-line chemotherapy with mitomycin C, 7 mg/m2 every 4 weeks, folinic acid 200 mg/m2/day as a 2 h infusion followed by 400 mg/m2 of 5FU bolus and 600 mg/m2 continuous 5FU infusion for 22 h on days 1 and 2 and every 14 days; 19 patients did not respond to folinic acid and 5FU bolus regimen (in 2 patients, this was associated with pirarubicin in a continuous hepatic artery infusion) and 3 did not respond to irinotecan; 2 patients had disease progression during adjuvant chemotherapy with folinic acid and 5FU bolus. Tumor response was assessed every 12 weeks. One patient died before evaluation and 1 was lost to follow-up after 3 cycles; 7/24 patients had an objective response (29.2%, 95% confidence interval (CI): 11.0-47.4) including 2 complete responses; 7 additional patients had stable disease or minor response. Mean duration of response was 7.5 months. Median survival was 10 months and survival at 1 year was 39.4% (95% CI: 4-59.4). One patient who had a disease progression under irinotecan presented an objective response. No iatrogenic deaths occurred, nor was any grade 3 or 4 myelotoxicity seen. No hand-foot syndrome nor any cardiotoxicity arose but 2 grade II alopecia were seen. Digestive toxicities were the most frequent but with only 4 grade III toxicities (1 vomiting, 1 mucositis and 2 diarrhea) and no grade IV. With nearly 30% objective response and acceptable toxicity this treatment seems to offer a good alternative in the treatment of advanced colorectal cancers after the failure of first-line chemotherapy.