Purpose The antiangiogenic agent aflibercept (ziv-aflibercept in the United States) in combination with 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) significantly improved survival in a phase III study of patients with metastatic colorectal cancer (mCRC) previously treated with an oxaliplatin-based regimen. In the present analysis, outcomes were evaluated in prespecified subgroups to assess the consistency of the treatment effect. Methods Patients were randomised to receive FOLFIRI plus aflibercept or placebo every 2 weeks until disease progression or unacceptable toxicity occurred. Efficacy and safety outcomes were analysed with respect to demographic and baseline characteristics, and stratification factors (prior bevacizumab treatment and Eastern Cooperative Oncology Group performance status). Results Median overall survival (OS, months [95.34% confidence interval (CI)]) for aflibercept versus placebo was 12.5 (10.8-15.5) versus 11.7 (9.8-13.8) in patients with prior bevacizumab treatment and 13.9 (12.7-15.6) versus 12.4 (11.2-13.5) in patients with no prior bevacizumab treatment. The p value for interaction was 0.5668, indicating there was no heterogeneity in these subgroups. For OS and progression-free survival (PFS), there was a significantly greater benefit (at the 2-sided 10% level) of treatment for patients with liver only metastases versus patients with no liver metastases/liver metastases with other organ involvement (p value for interaction: 0.0899 [OS]; 0.0076 [PFS]). There was no evidence of heterogeneity in treatment effect in any of the other subgroups examined. Conclusions The benefits of aflibercept in combination with FOLFIRI in patients with mCRC previously treated with oxaliplatin were maintained across the specified patient subgroups, including in patients with or without prior bevacizumab treatment. © 2013 Elsevier Ltd. All rights reserved.