We administered hepatic arterial infusion chemotherapy (HAIC) prior to FOLFOX to three patients with unresectable liver metastases from colorectal cancer. The patients' disease state was found to be highly advanced based on both computed tomography findings and liver function tests. The treatment strategy included an initial administration of HAIC to control liver metastases and improve liver function in order to facilitate the subsequent safe administration of FOLFOX without drug loss. As the HAIC regimen, 1,000 mg/m2 of 5-FU was administered weekly by continuous 5-h infusion after performing laboratory investigations through an implanted port-catheter system. After 3 HAIC cycles administered over 3 consecutive weeks, the mean alkaline phosphatase levels decreased from 969.3IU/l to 422IU/l due to shrinkage of the liver metastases. Thereafter, FOLFOX without drug loss could be safely initiated for all patients. Two patients succumbed 488 and 333 days after HAIC was initiated;the third patient is still alive and has been followed-up for 1215 days. The combined use of HAIC and standard systemic chemotherapy could be a feasible and efficacious treatment in highly advanced cases of liver dysfunction.