Background: Glioblastoma (GBM) is highly vascularized tumor with elevated expression of vascular endothelial growth factor (VEGF). Bevacizumab (Bz) is a humanized monoclonal antibody against VEGF, which alone or associated with chemotherapy has obtained optimal results. However, the most suitable combination with bevacizumab is yet unknown. The objective of our study is to evaluate the efficacy and safety of Bz and fotemustine (Ft) in patients (pts) with recurrent GBM of the Huelva area and to compare our results with those published in the phase II study of the Italian Association of Neuro-oncology (AINO). Methods: Observational and descriptive study of the combination of Ft-Bz in GBM at first relapse after standard radiotherapy and TMZ concomitant in the hospital area of Huelva during the years 2010-2021. We used the same therapeutic scheme of the phase II study of AINO and the IBM SPSS Statistics 22 program to analyze the variables. Results: 42 pts were treated, 16 women and 25 men. Median age 52 years. ECOG 0-1 in 85.4%. 65.9% and 92.7% received antiepileptics and corticosteroids, respectively. In 90.2%, methylation status of the promoter of O⁶-methylguanine-DNA methyltransferase (MGMT) was not evaluated. Previously, 56.1% of the pts underwent total/subtotal resection, 29.3% partial and 14.6% were not resected, followed by concomitant radiotherapy and temozolamide in 100% of cases. 35.7% relapsed in less than 3 months after adjuvant treatment. 61% presented unifocal relapse and 39% multifocal. 46.3% of the pts had stable disease, 24.4% partial response and 2.4% complete response. 22% presented grade 3-4 toxicity. The most frequent toxicities are listed in the table. The median progression-free survival (PFS) was 6 months (95% CI 4.18-7.82) and the median overall survival (OS) was 7 months (95% CI 4.22-9.77). Conclusions: The results obtained in our study were similar to those of other previously published studies of Bz in combination with Ft. Although PFS was slightly higher than the phase II study AINO, OS was lower, probably due to the inclusion of a high rate of rapid progressors pts. Treatment tolerance was similar to that in the phase II study AINO. An increase in hematologic adverse events stands out in our pts. Therefore, this scheme can be a valid alternative in the management of recurrent GBM.