The clinical efficacy and safety of irinotecan plus infusional fluorouracil/l-leucovorin (FOLFIRI) in patients with fluoropyrimidine-resistant metastatic colorectal cancer were studied retrospectively. 20 patients were treated with FOLFIRI at our hospital between October 2003 and November 2005. The objective overall response rate was 28% (5/18; 95% confidence interval, 9.7-54%). The disease control rate (CR+PR+SD) was 61%. The most frequent grade 3 to 4 adverse event was neutropenia, and it was seen in 50%. Non-hematological toxicities were mild. The median survival time was 11 months. The 1-year survival rate was 34%. This study showed the activity and safety of FOLFIRI in practice.