Glioblastoma multiforme is a malignant central nervous system (CNS) disease with dismal prognosis. Current treatment modalities only offer modest activity and usually of short duration, so there is an urgent need for the conduct of clinical trials exploring new treatment options and modalities. The vincristine-irinotecan-temozolomide and bevacizumab (VITb) regimen is an option of special interest, as it has produced encouraging results in young patients with various relapsed/refractory childhood and adolescence solid tumors, with an acceptable toxicity profile. With the current report, we present the case of a young male patient who was treated for GBM in second relapse at out institution, after previous surgical attempts and two radiotherapy sessions in conjunction with temozolomide and experienced a major and long-lasting response, weaned off steroids, to the VITb regimen followed by bevacizumab maintenance. The above case is discussed in the context of the existing literature regarding available evidence of synergy between the drugs used and the activity of certain components of the combination (i.e. combination of temozolomide-irinotecan ± vincristine, or bevacizumab-irinotecan in GBM) or the complete VITb regimen in other pediatric/adolescence solid tumors and the few cases reported with GBM.