Background: Compared with systemic therapy, hepatic arterial infusion (HAI) increases the response to fluoropyrimidines. Methods: Thirty-one patients with non-resectable, colorectal cancer (CRC) liver metastases received irinotecan 120 mg/m2, followed by leucovorin (LV) 20 mg/m2 and 5-fluorouracil (5-FU) 500 mg/m2 administered by HAI every 2 weeks, plus UFT (tegafur-uracil) 200 mg/m2/day with LV 30 mg/day on days 1–22, followed by a 6-day rest. Results: The objective response rate was 65% (all 20 patients achieving a partial response). Ten patients (32%) had stable disease. The median time to progression (TTP) and overall survival (OS) were 12 and 36 months. OS was similar in patients with low versus high expression of thymidylate synthase (TS) and/or dihydropyrimidine dehydrogenase (DPD). The regimen was well tolerated. Conclusions: UFT with LV plus HAI irinotecan and 5-FU/LV was a feasible and effective treatment for non-resectable CRC liver metastases, increasing response, TTP and OS. TS and DPD levels in liver metastases did not predict outcome. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]