I will assume that by "move the box towards the middle", you want the boxes to be vertically centered on the math axis. (Aside: The math axis is an invisible horizontal line that bisects symbols such as -
, =
, and +
.) Moreover, I will assume that you'd like to achieve this goal without enlarging the frameboxes.
If these assumptions are correct, I suggest you encase the frameboxes in \vcenter{\hbox{...}}
wrappers; \vcenter
is a command that centers its argument vertically on the math axis.
By the way, I think it's easier to write \boxed{}
than \fcolorbox{black}{white}{\null}
.

\documentclass{article}
\usepackage{enumitem,multicol,xcolor,amsmath}
\fboxsep=4mm \fboxrule=0.5mm
\newcommand\mybox{%
\vcenter{\hbox{$\boxed{}$}}} % feel free to come up with a snazzier name
\begin{document}
\noindent \textcolor{red}{Before}
\begin{multicols}{3}
\begin{enumerate}[label=(\alph*)]
\item $2 + \boxed{} = 5$
\item $\boxed{} + 2 = 5$
\item $1 + \boxed{} = 5$
\item $\boxed{} + 1 = 5$
\item $3 + \boxed{} = 5$
\item $\boxed{} + 3 = 5$
\end{enumerate}
\end{multicols}
\bigskip
\noindent \textcolor{red}{After}
\begin{multicols}{3}
\begin{enumerate}[label=(\alph*)]
\item $2 + \mybox = 5$
\item $\mybox + 2 = 5$
\item $1 + \mybox = 5$
\item $\mybox + 1 = 5$
\item $3 + \mybox = 5$
\item $\mybox + 3 = 5$
\end{enumerate}
\end{multicols}
\end{document}