I’d recommend flexbox. When you build mobile app with react native, the understanding of flexbox would be very useful since React Native use flexbox instead of grid. You can’t use grid in React Native since RN uses Apple Native UIKit which use flexbox instead of grid
Flexbox support is pretty good since most people use chrome/firefox/safari. From my experience, the only most troublesome thing is setting up the auto-prefixer correctly, because the 2009 Syntax display: -webkit-box; /* OLD - iOS 6-, Safari 3.1-6, BB7 */ breaks google bot rendering.
My latest auto-prefixer settings in my meteor project is set to "browsers": ["last 2 versions", "safari > 6"], which gives you the most you need, but no IE prefixes.