BACKGROUND: Short-term infusion of 5-fluorouracil with leucovorin in combination with irinotecan or oxaliplatin has been considered as standard treatment for metastatic colorectal cancer. However, until infusion of 5-fluorouracil regimens and oxaliplatin was approved for the treatment of metastatic colorectal cancer in Japan early in 2005, combination of irinotecan with bolus 5-fluorouracil/leucovorin had been the standard treatment. This retrospective study evaluates the efficacy and safety of a modified irinotecan with bolus 5-fluorouracil/leucovorin regimen in Japanese colorectal cancer patients. METHODS: Forty-six patients untreated with chemotherapy for metastatic colorectal cancer received a modified form of the irinotecan with bolus 5-fluorouracil/leucovorin regimen, consisting of intravenous irinotecan (100 mg/m2) and l-leucovorin (10 mg/m2), and then 5-fluorouracil 500 mg/m2 as an intravenous bolus infusion, weekly for 4 weeks, repeated every 6 weeks until progression or unacceptable toxicity. RESULTS: The overall response rate was 48% (95% confidence interval, 34-62%), and 48% of patients had stable disease. Median progression-free survival was 8.3 months and overall survival was 20.3 months. The incidence of grade 3 or 4 toxicity was as follows: neutropenia, 50%; diarrhea, 4%; fatigue, 13%; nausea, 7%; and vomiting, 7%. Neither treatment-related nor all-cause mortality occurred within 60 days of chemotherapy initiation. Despite the limited availability of oxaliplatin, 29 patients received an oxaliplatin-based regimen after progression. CONCLUSION: A modified irinotecan plus bolus 5-fluorouracil/l-leucovorin regimen was an active and well-tolerated regimen in Japanese patients with advanced colorectal cancer, showing a different toxicity profile from Western patients.