The clinical efficacy and safety of irinotecan (CPT-11) therapy were studied retrospectively in patients with fluoropyrimidine-resistant advanced colorectal cancer. The subjects were 44 patients who were treated with CPT-11 alone or with a combination of CPT-11 and mitomycin C (MMC) at our institute from April 1999 to March 2003. CPT-11 (120-150 mg/m2) alone or CPT-11 with MMC (5 mg/m2) was administered every 2 weeks. The objective overall response rate was 11% (95% confidence interval, 3.8-25%). In 38 patients who were treated until October 2002, the median survival time was 12 months. Two-year survival rate was 13%. Grade 3 anorexia or diarrhea occurred in 6 patients (14%) and 5 patients (11%), respectively. There was no treatment-related death or early death within 30 days from the last administration of CPT-11 (+MMC). This retrospective study demonstrated the reproducible activity and safety of CPT-11 for the treatment of fluoropyrimidine-resistant advanced colorectal cancer in clinical practice.