The role of irinotecan-based chemotherapy as induction treatment of non-resectable advanced colorectal cancer (ACRC) is currently being elucidated. The objective of this retrospective study was to determine complete resection (R0), response rate, time to progression (TTP) and overall survival (OS) in patients with non-resectable ACRC after being treated with neoadjuvant irinotecan-based chemotherapy. Thirty-six patients with ACRC were selected, of whom 23 (64%) were treated with irinotecan (250 mg/m2 on day 1), UFT (300 mg/m2/day for 14 days) plus leucovorin (45 mg/day for 14 days) every 3 weeks. Another 13 (36%) received the FOLFIRI schedule of irinotecan plus 5-fluorouracil/leucovorin. A total of 214 cycles of irinotecan/UFT/LV (median 8, range 1-15) and 97 cycles of the FOLFIRI schedule (median 9, range 1-30) were administered. The overall response rate was 58% (95% confidence interval 42-74), with six complete and 15 partial responses, whereas seven patients (19%) showed stable disease. Laparotomy was performed in 12 patients, of whom eight (22%) achieved R0 and two (6%) a pathological complete response. Median TTP was 10.0 months and median OS was 38.0 months for all patients. After a median follow-up of 20 months (range 1-49), median TTP in patients with R0 was not reached (mean TTP, 33.1 months), whereas median TTP in non-resected patients was 7.5 months (p=0.016). Toxicity was manageable and no toxic deaths occurred. This retrospective study showed a high resectability rate, and a prolonged TTP and OS in patients with ACRC after induction treatment with irinotecan-based chemotherapy. Both toxicity profile and postoperative complications were acceptable. Nevertheless, the definitive role of irinotecan as induction treatment should be confirmed in future clinical trials.