We present two cases of multiple liver metastases from colorectal cancer, which did not respond to hepatic arterial infusion (HAI) using 5-fluorouracil (5-FU 1250 mg/body weekly) alone, but responded to HAI using 5-fluorouracil (5-FU 750 mg/body weekly) and l-leucovorin (l-LV 50 mg/body weekly) achieving a complete response (CR). The first case: A 71-year-old man with Stage II rectal cancer who underwent lower anterior resection developed multiple liver metastases 5 months after the surgery. As the weekly HAl using 5-FU for nine courses showed no response, l-LV was combined, and the liver metastases disappeared after 10 courses to achieve CR. The second case: A 65-year-old man with rectal cancer, sigmoid colon cancer and multiple liver metastases underwent lower anterior resection. The weekly HAl using 5-FU for seven courses showed no response. By combining 5-FU to l-LV, the liver metastases disappeared after fifteen courses. No toxic event was observed. In these two cases, it was suspected that a reduced foliate may be responsible for the failure by the 5-FU treatment alone.