In summary, we reported that WASHC4, HELZ, ERN1, RPS6KB1, and APPBP2 were downregulated, while IRF7, EML3, LYPLA2, DRAP1, RNH1, PKP3, TSPAN17, LSS, MLKL, PPP1R7, GCDH, C19ORF24, and CCDC124 were upregulated in FOLFOX responders compared with nonresponders in metastatic or recurrent CRC patients, and those genes could be potential therapeutic targets for FOLFOX‐resistant metastatic CRC. This evidence concerns the gene LYPLA2 and colorectal carcinoma.