To treat colorectal liver metastases, intra-arterial chemotherapies may complete therapeutic arsenal. Drugs using intra-arterially are very heterogeneous. The aim of this study was to select the most efficient drug on a panel of colorectal cancer (CRC) cell lines (Caco-2, HCT 116, HT 29, SW 48, SW 480, SW 620) exposed for 30 min to 12 cytotoxic agents (doxorubicin, epirubicin, idarubicin, 5-FU, raltitrexed, gemcitabine, cisplatin, oxaliplatin, mitomycin C, irinotecan, streptozocin, paclitaxel) at different concentrations. The effect on cell viability was measured using the WST-1 cell viability assay. For each drug and cell line, the IC50 and IC90 were calculated, which respectively correspond to the drug concentration (mg/mL) required to obtain 50% and 90% of cell death. We also quantified the cytotoxic index (CyI90 = C Max/IC90) to compare drug efficacy. The main findings of this study are that idarubicin emerged as the most cytotoxic agent to most of the tested CRC cell lines (Caco-2, HT29, HCT116, SW620 and SW480). Gemcitabine seemed to be the most efficient chemotherapy for SW48. Interestingly, the most commonly used cytotoxic agents in the systemic and intra-arterial treatment of colorectal liver metastasis (CRLM) (oxaliplatin, 5-FU, irinotecan) showed very limited cytotoxicity to all the cell lines.