Background: Colorectal cancer is currently the third most common cancer worldwide. The results of the VELOUR study showed that the addition of aflibercept to Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) produced an advantage in both progression-free and overall survival (PFS and OS) in patients with metastatic colorectal cancer (mCRC) previously treated with an oxaliplatin-based regimen. The purpose of this study was to evaluate the efficacy and safety of the combination of aflibercept with FOLFIRI in patients aged 70 years and older with mCRC. Methods: We conducted a retrospective multicenter study, which included all patients aged 70 years and older with mCRC treated with Aflibercept plus FOLFIRI between May 2013 and March 2019 in 5 centers in Spain. Data regarding clinical and pathological characteristics, treatment response and survival were collected. Results: We selected 69 patients, of whom the majority (n = 48, 69.6%) were males with a median age of 75 years (range 70 to 84 years). Patients received an average of nine courses of aflibercept with FOLFIRI overall. Regarding response rates, 17 patients (24.6%) achieved a partial response, 37 (53.6%) had stable disease and 15 (21.7%) experienced disease progression. The median PFS was 6.1 months (CI 95%: 4.4–7.8), and the median OS was 13.9 months (CI 95%: 11.1–16.7). Treatment adverse events grade 3 and 4 were reported in 42 patients (60.9%). The most frequently reported treatment adverse events grade 3 and 4 were asthenia (24.6%), diarrhea (18.8%), stomatitis and ulceration (18.8%) and neutropenia (14.5%). Adverse events grade 3 and 4 typically associated with anti-VEGF therapy were infrequent. Adverse events led to permanent discontinuation of treatment in 26.1% of patients. Conclusions: In our sample the combination of aflibercept with FOLFIRI in patients aged 70 years and older with mCRC was effective and safe. Aflibercept plus FOLFIRI is a good therapeutic option for the treatment of mCRC in patients aged 70 years and older previously treated with oxaliplatin.