Aim: We report a prospective randomized study comparing survival, response and toxicity in colorectal liver metastasis (CLM) patients treated by either hepatic arterial floxuridine (HAI) plus continuous systemic fluorouracil/folinic acid or systemic fluorouracil/folinic acid. Methods: Eighty-four CLM patients received either HAI plus systemic fluorouracil/folinic acid or systemic fluorouracil/folinic acid. Results: Significantly more HAI plus systemic, compared with systemic only, patients developed WHO grade 3 or 4 diarrhoea (P=0.004), but significant quality of life differences were not detected. Liver metastasis partial response at 4 months after randomization was significantly greater (P=0.003) in HAI plus systemic (13/29, 45%) compared with systemic only (7/30, 23%) patients. There was no significant difference between groups in the proportion of patients who died from extrahepatic disease progression, or in survival. Conclusion: Combining regional with systemic fluorinated pyrimidines did not improve survival compared with systemic fluorinated pyrimidine.