This association was further confirmed in a second validation cohort comprising refractory mCRC patients treated with cetuximab ± irinotecan (PFS 8.7 vs. 3.7 months) in univariable (<i>P</i> = 0.033) and multivariable analyses (<i>P</i> = 0.046).<b>Conclusions:</b><i>GC</i> rs4588 SNP might serve as a predictive marker in mCRC patients treated with FOLFIRI/bevacizumab or FOLFIRI/cetuximab.