The aim of this study was to assess the activity and safety of bevacizumab (BEV) and fotemustine (FTM) for the treatment of recurrent glioblastoma multiforme (GBM) patients and explore the potential prognostic parameters on survival. This study retrospectively analyzed all patients with GBM who were treated with at least one cycle of BEV and FTM from July 2010 to October 2012. A total of 176 patients with recurrent GBM were enrolled. The response rate and disease control rate were 46.6% and 90.9%, respectively. A 6-month PFS rate of 33.3% (95% CI: 26.5%-40.3%) and a median PFS of 5.0 (95% CI: 2.4-7.5) months were observed. The median OS was 8.0 (95% CI: 6.7-9.2) months. Multivariate analysis showed that risk factors with a significant influence on the PFS of all patients were Karnofsky Performance Status (KPS) (>= 70 versus <70, HR = 0.53, 95% CI: 0.39-0.73, and P = 0.01) and MGMT status (methylated versus unmethylated, HR = 0.69, 95% CI: 0.52-0.97, and P = 0.04). The most common treatment-related adverse events were fatigue, proteinuria, hypophonia, hypertension, thrombocytopenia, anemia, and neutropenia. In conclusion, combination of BEV with FTM is well tolerated and may derive some clinical benefits in recurrent GBM patients. Higher KPS and MGMT promoter hypermethylation were suggested to be associated with prolonged survival.