Abstract Objectives To describe the response to IL-6 blockade tocilizumab (TCZ) in three patients affected by highly refractory neuro-Behçet disease (NBD). Methods Three patients who had failed synthetic immunosuppressants and TNF-α antagonists combined with glucocorticoids received TCZ after obtaining their informed consent. Two patients underwent TCZ infusions at 8 mg/kg every 4 weeks for a mean period of 24 months, while in one patient, the frequency of TCZ infusions was increased to every other week after 21 months due to a disease flare. Concomitant therapy with synthetic agents and low-to-medium dose glucocorticoids was continued. Clinical and imaging findings were assessed before and after the onset of TCZ therapy. Results In all our patients, a very short time lag between the onset of treatment with TCZ and the clinical response was observed. A partial response occurred in two patients and a nearly complete response in one. Some loss of efficacy occurred after 18 months in one patient, but there was again a significant improvement when the interval between the infusions was shortened. TCZ was overall well tolerated and no serious adverse events occurred. In two patients, the prednisone dose could successfully be tapered to about 20 mg/day, while in another patient glucocorticoids could safely be withdrawn. Brain MRI remained virtually unchanged in all patients. Conclusions Although TCZ has not yet been included among the medications recommended for the treatment of NBD, our data suggest that it may be considered for patients with refractory NBD.