Ultracold polar molecules possess long-range, anisotropic, and tunable dipolar interactions, providing unique opportunities to probe novel quantum phenomena 1-4 . However, experimental progress has been hindered by excessive two-body loss, which also limits further cooling via evaporation. Recent work shows the loss can be mitigated by confining molecules in a two-dimensional geometry 5,6 . However, a general approach for tuning molecular interactions in a full three-dimensional (3D) stable system has been lacking. Here, we demonstrate the use of an electric field-induced shielding resonance [6][7][8] to suppress the reactive loss by a factor of 30 while preserving elastic, long-range dipolar interactions in a bulk gas of ultracold 40 K 87 Rb molecules in 3D. The favorable ratio of elastic to inelastic collisions enables direct thermalization, the rate of which depends on the angle between the collisional axis and the dipole orientation controlled by an external electric field. This is a direct manifestation of the anisotropic dipolar interaction. We further achieve dipolar-interaction-mediated evaporative cooling in 3D. This work demonstrates control of a long-lived bulk quantum gas system with tunable long-range interactions, paving the way for the study of collective quantum many-body physics.